In the fruit fly Drosophila melanogaster, there are eight insulin-like peptides (DILPs) with DILPs 1–7 interacting with a sole insulin-like receptor tyrosine kinase (DInR) while DILP8 interacts with a single G protein-coupled receptor (GPCR), Lgr3. Loss-of-function dilp mutation studies show that the neuropeptide DILP2 has a key role in carbohydrate and lipid metabolism as well as longevity and reproduction. A better understanding of the processes whereby DILP2 mediates its specific actions is required. Consequently we undertook to prepare DILP2 as part of a larger, detailed structure–function relationship study. Use of our well established insulin-like peptide synthesis protocol that entails separate solid-phase assembly of each of the A- and B-chains with selective cysteine S-protection followed by sequential S-deprotection and simultaneous disulfide bond formation produced DILP2 in good overall yield and high purity. The synthetic DILP2 was shown to induce significant DInR phosphorylation and downstream signalling, with it being more potent than human insulin. This peptide will be a valuable tool to provide further insights into its binding to the insulin receptor, the subsequent cell signalling, and role in insect metabolism.

在果蝇果蝇中，有八个胰岛素样肽（DILP），其中DILP 1–7与唯一的胰岛素样受体酪氨酸激酶（DInR）相互作用，而DILP8与单个G蛋白偶联受体（GPCR）相互作用， Lgr3。功能丧失Dilp突变研究表明，神经肽DILP2在碳水化合物和脂质代谢以及寿命和繁殖中起关键作用。需要更好地了解DILP2介导其特定动作的过程。因此，我们承诺准备DILP2作为更大，详细的结构-功能关系研究的一部分。使用我们已建立的胰岛素样肽合成方案，该方案需要对每个A链和B链进行单独的固相组装，并进行选择性半胱氨酸S-保护，然后依次进行S-去保护和同时形成二硫键，从而产生了良好的DILP2产量高，纯度高。已显示合成的DILP2诱导显着的DInR磷酸化和下游信号传导，比人胰岛素更有效。